X-139738013-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001353812.2(ATP11C):c.3191T>G(p.Val1064Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 23)
• Consequence: ATP11C NM_001353812.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.34

Genes affected

ATP11C (HGNC:13554): (ATPase phospholipid transporting 11C) Enables phosphatidylethanolamine flippase activity and phosphatidylserine flippase activity. Predicted to be involved in phospholipid translocation; positive regulation of B cell differentiation; and pre-B cell differentiation. Located in endoplasmic reticulum and plasma membrane. Is integral component of plasma membrane. Implicated in X-linked congenital hemolytic anemia. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.26870996).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ATP11C	NM_001353812.2	c.3191T>G	p.Val1064Gly	missense_variant	28/30	ENST00000682941.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ATP11C	ENST00000682941.1	c.3191T>G	p.Val1064Gly	missense_variant	28/30		NM_001353812.2	A1

Frequencies

GnomAD3 genomes Cov.: 23

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 23

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 26, 2023

The c.3200T>G (p.V1067G) alteration is located in exon 28 (coding exon 28) of the ATP11C gene. This alteration results from a T to G substitution at nucleotide position 3200, causing the valine (V) at amino acid position 1067 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.040
Cadd	Benign	19
Dann	Benign	0.87
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.42	T;T;T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Benign	0.27	T;T;T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.1	N;N;N;N
REVEL	Benign	0.25
Sift	Benign	0.33	T;T;T;T
Sift4G	Benign	0.63	T;T;T;T
Polyphen		0.0040, 0.0060	.;B;B;.
Vest4		0.31
MutPred		0.63		.;Loss of stability (P = 0.0051);Loss of stability (P = 0.0051);.;
MVP		0.92
MPC		1.4
ClinPred		0.63	D
GERP RS		6.0
Varity_R		0.71
gMVP		0.76

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chrX-138820172;